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Abstract
The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.
Highlights
The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium
Three pairs of total RNAs derived from basal and luminal populations were generated for library preparations and subsequent RNA sequencing (RNA-Seq)
By applying a stringent statistic threshold of greater than equal to twofold change (FC) and false discovery rate (FDR) of o0.05, we identified a consensus of 853 differentially expressed genes (DEGs) upregulated in basal and 940 DEGs in luminal cells (Supplementary Data 1)
Summary
The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. An in-depth understanding of the gene-expression differences in normal human prostate basal versus luminal cells could help illuminate the intrinsic functional differences between the two cell types, which, in turn, could offer fresh insights into the cell-of-origin for (different types of) PCa. Gene expression is a key determinant of cellular phenotypes. We describe a detailed transcriptome analysis of unperturbed human benign prostatic basal and luminal cells by deep RNA-Seq. The results reveal the surprising findings that basal cells are intrinsically enriched in gene sets normally associated with SCs, neurogenesis and ribosomal RNA (rRNA) biogenesis. Our results provide the most functionally comprehensive study on, and a resource of the transcriptomes in, unperturbed subtypes of human prostatic epithelial cells that shed light on PCa aetiology
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